[Development of reverse tolerance to the ambulation-increasing effect of ephedrine after repeated administration in...

Effects of repeated administration of ephedrine (EPH) 40 and 80 mg/kg sc, and 20, 40, and 80 mg/kg ip on ambulatory activity in adult male mice of the dd strain were investigated. The drug was administered 5 times at intervals of 1 and 7 days. The ambulatory activity of each mouse was measured by a tilting-type round activity cage of 25 cm in diameter for 150-210 min after the drug administration. Repeated administration of EPH 80 mg/kg ip produced a marked augmentation in the sensitivity of the mouse, i.e. reverse tolerance, to the ambulation-increasing effect of the drug regardless of the administration intervals. However, repeated administration of 80 mg/kg sc and 40 mg/kg ip at intervals of 7 days caused a slight reverse tolerance, while 40 mg/kg sc at intervals of 7 days as well as 20 and 40 mg/kg ip at intervals of 1 day did not produce reverse tolerance. In contrast, a poorer development of reverse tolerance to the ambulation-increasing effect of EPH was observed when a mouse was confined in a glass jar of 5 cm in diameter to impede ambulation for 150-180 min after each administration. Mice showing reverse tolerance to EPH demonstrated an increased sensitivity to methamphetamine as compared with the saline-pretreated control mice. The present results suggest that the characteristics of reverse tolerance to ambulation-increasing effect of EPH are almost identical with those after methamphetamine and methylphenidate.